Jeremy Hogeveen1, Marie K Krug2, Matthew V Elliott2, Marjorie Solomon3. 1. MIND Institute, University of California, Davis, Sacramento, California; Department of Psychiatry and Behavioral Sciences, University of California, Davis, Sacramento, California. Electronic address: hogeveen@ucdavis.edu. 2. MIND Institute, University of California, Davis, Sacramento, California; Department of Psychiatry and Behavioral Sciences, University of California, Davis, Sacramento, California. 3. MIND Institute, University of California, Davis, Sacramento, California; Department of Psychiatry and Behavioral Sciences, University of California, Davis, Sacramento, California; Imaging Research Center, University of California, Davis, Sacramento, California.
Abstract
BACKGROUND: Internalizing symptoms like anxiety and depression are common and impairing in autism spectrum disorder (ASD). Here, we test the hypothesis that aberrant functional connectivity among three brain networks (salience network [SN], default mode network [DMN], and frontoparietal network [FPN]) plays a role in the pathophysiology of internalizing in ASD. METHODS: We examined the association between resting-state functional connectivity and internalizing in 102 adolescents and young adults with ASD (n = 49) or typical development (n = 53). Seed-to-target functional connectivity was contrasted between adolescents and young adults with ASD and typically developing subjects using a recent parcellation of the human cerebral cortex, and connections that were aberrant in ASD were analyzed dimensionally as a function of parent-reported internalizing symptoms. RESULTS: Three connections demonstrated robust overconnectivity in ASD: 1) the anterior insula to the retrosplenial cortex (i.e., SN-DMN), 2) the anterior insula to the frontal pole (i.e., SN-FPN), and 3) the dorsolateral prefrontal cortex to the retrosplenial cortex (i.e., FPN-DMN). These differences remained significant after controlling for age, and no age-related effects survived correction. The SN-DMN connection was associated with greater internalizing in ASD, mediated by a bigger difference between self- and parent-reported internalizing. Control analyses found that the other two connections were not associated with internalizing, and SN-DMN connectivity was not associated with a well-matched control measure (externalizing symptoms). CONCLUSIONS: The present findings provide novel evidence for a specific link between SN-DMN overconnectivity and internalizing in ASD. Further, the mediation results suggest that intact anterior insula-retrosplenial connectivity may play a role in an individual's generating insight into his or her own psychopathology.
BACKGROUND: Internalizing symptoms like anxiety and depression are common and impairing in autism spectrum disorder (ASD). Here, we test the hypothesis that aberrant functional connectivity among three brain networks (salience network [SN], default mode network [DMN], and frontoparietal network [FPN]) plays a role in the pathophysiology of internalizing in ASD. METHODS: We examined the association between resting-state functional connectivity and internalizing in 102 adolescents and young adults with ASD (n = 49) or typical development (n = 53). Seed-to-target functional connectivity was contrasted between adolescents and young adults with ASD and typically developing subjects using a recent parcellation of the human cerebral cortex, and connections that were aberrant in ASD were analyzed dimensionally as a function of parent-reported internalizing symptoms. RESULTS: Three connections demonstrated robust overconnectivity in ASD: 1) the anterior insula to the retrosplenial cortex (i.e., SN-DMN), 2) the anterior insula to the frontal pole (i.e., SN-FPN), and 3) the dorsolateral prefrontal cortex to the retrosplenial cortex (i.e., FPN-DMN). These differences remained significant after controlling for age, and no age-related effects survived correction. The SN-DMN connection was associated with greater internalizing in ASD, mediated by a bigger difference between self- and parent-reported internalizing. Control analyses found that the other two connections were not associated with internalizing, and SN-DMN connectivity was not associated with a well-matched control measure (externalizing symptoms). CONCLUSIONS: The present findings provide novel evidence for a specific link between SN-DMN overconnectivity and internalizing in ASD. Further, the mediation results suggest that intact anterior insula-retrosplenial connectivity may play a role in an individual's generating insight into his or her own psychopathology.
Authors: Jeffrey D Rudie; Zarrar Shehzad; Leanna M Hernandez; Natalie L Colich; Susan Y Bookheimer; Marco Iacoboni; Mirella Dapretto Journal: Cereb Cortex Date: 2011-07-22 Impact factor: 5.357
Authors: Benjamin E Yerys; Birkan Tunç; Theodore D Satterthwaite; Ligia Antezana; Maya G Mosner; Jennifer R Bertollo; Lisa Guy; Robert T Schultz; John D Herrington Journal: Biol Psychiatry Cogn Neurosci Neuroimaging Date: 2019-01-09
Authors: Jeremy Hogeveen; Marie K Krug; Raphael M Geddert; J Daniel Ragland; Marjorie Solomon Journal: Biol Psychiatry Cogn Neurosci Neuroimaging Date: 2019-09-05
Authors: Andrew Gordon; Marie K Krug; Rachel Wulff; Matthew V Elliott; Jeremy Hogeveen; Tyler Lesh; Cameron Carter; Marjorie Solomon Journal: Biol Psychiatry Cogn Neurosci Neuroimaging Date: 2020-11-26